Long-Term T Cell Responses in the Ischemic Brain

Stroke is a debilitating and devastating disorder with significant annual mortality and morbidity rates worldwide. Following ischemic injury, blood-brain barrier integrity is disrupted and multiple inflammatory cascades are initiated both in the central nervous system and in the peripheral immune system. These early inflammatory responses result in the recruitment of systemic immune cells into the brain parenchyma. T lymphocytes, part of the adaptive arm of the immune response, are present bordering the infarct region within days after stroke. Accumulation of these cells in the early inflammatory phase peaks 3 to 4 days after stroke injury. However, T cells persists as late as 7 weeks post-stroke and it is unclear if they are beneficial or detrimental to functional recovery in this chronic phase post-stroke. We found significant numbers of CD4 T cells and CD8 T cells in the brain parenchyma long-term post-stroke. These long-term CD8 T cells were mainly present in the injured tissue area and potentially function through IFN-g secretion. We further determined that the long-term post-stroke CD8 T cells affected inflammation and functional recovery post-stroke. CD8 T cell-depleted mice demonstrated better recovery in the rotarod behavior test and had fewer immune cells recruited to the brain parenchyma post-stroke. We also observed the presence of CNS-specific T cells in the post-stroke spleens and cervical lymph nodes. Taken together, these data reveal a role for CD8 T cells in the chronic phase post-stroke that can be therapeutically targeted. Furthermore, long-term post-stroke immune cells in the brain parenchyma regulate chronic inflammatory responses and functional recovery after stroke.